Transient receptor potential cation channel vanilloid (TRPV) 4 in ventilator‐induced lung injury (VILI)
Bibliographic record
Abstract
Study objective Ca 2+ entry via TRPV4 has been implicated in stretch‐induced barrier failure in isolated lungs. Here, we assessed the relevance of TRPV4 in VILI in vivo , and probed for the contribution of serum/glucocorticoid‐regulated kinase (SGK) 1, which phosphorylates TRPV4, and of Ca 2+ ‐activated K + channels (SK, BK) as putative signalling mechanisms upstream and downstream of TRPV4, respectively. Methods Male, anesthetized mice were mechanically ventilated for 2 h by low (7 ml/kg) and high (20 ml/kg) tidal volumes (LV T /HV T ) in wild type and TRPV4‐deficient mice, and following pharmacological inhibition of SGK1, TRPV4, SK or BK channels. Results TRPV4 deficiency or inhibition by HC‐067047 attenuated VILI as demonstrated by reduced lung edema, protein leak, MPO activity, inflammatory cytokine levels, and histological features of lung injury. Inhibition of SK or BK channels by apamin or charybdotoxin attenuated lung edema in HV T mice, yet only charybdotoxin had concomitant anti‐inflammatory effects. Lung edema formation in HV T mice was also largely reduced by the SGK1 inhibitor GSK650394. Conclusions Here, we demonstrate the critical role of TRPV4 for VILI in vivo , and identify potential upstream (SGK1) and downstream (SK, BK) signalling events that may present putative pharmacological targets for the prevention or treatment of ventilator‐associated lung disease.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".